DESCRIPTION (Applicant's abstract): The extrathoracic airways influence breathing a great deal, but their physiology has been neglected until fairly recently. The purpose of this project since its inception has been to explore and define the influence of the upper airways on the control of breathing. This revised application seeks renewed support for this project to enable us to follow up exciting discoveries made during the previous funding period. We have demonstrated that spontaneous contractions of the urinary bladder and elevations of carotid sinus pressure are capable of markedly inhibiting breathing, and that in some circumstances, this inhibition is expressed much more strongly in the motor output to upper airway muscles than in that to the diaphragm. This pattern of inhibition not only reduces ventilatory effort, but also favors upper airway obstruction by pharyngeal collapse during inspiration. Inhibition of inspiration by signals from the bladder acts synergistically with inhibition due to lung inflation, so that animals held at high lung volume by positive end-expiratory pressure (PEEP) may become apneic for many seconds during spontaneous bladder contractions. We intend to examine this combination of stimuli systematically in decerebrate cats and to determine, in both cats and human subjects, the individual and combined inhibitory effectiveness of bladder contractions, PEEP and carotid sinus baroreceptor stimulation under various conditions of respiratory chemostimulation. Our underlying general hypothesis is that such little recognized respiratory inhibitory stimuli as bladder pressure and carotid baroreceptor stimulation may combine in some circumstances to cause clinically significant disturbances of breathing.